Most organophosphorus pesticides are direct inhibitors or are rapidly converted to inhibitors of acetylcholinesterase. A few of these compounds produce delayed neurotoxicity. The latter syndrome was first demonstrated in man; later, some species (cats and chickens) were found to be susceptible, while others were not (rodents and some primates). The test animal chosen to study this effect has been the adult chicken. The clinical condition becomes manifest first as ataxia, followed by paralysis. Lesions are characterized by degeneration of axons with subsequent secondary degeneration of myelin. Recently, DEF(S,S,S-tributyl phosphorotrithioate), a pesticide which includes delayed neurotoxicity in hens, was shown to cause a novel effect which we termed "late acute" effect (81). It caused lysis of red blood cells, loss of appetite and weight, weakness, emaciation lysis and death, and is neither relieved by atropine sulfate nor associated with histo-pathological changes in nerve tissues. The purpose of this study is to examine the delayed neurotoxic and late acute effect of DEF. Light and electron microscopic examination of the peripheral and central nervous systems will allow us to determine the extent and pattern of nervous system damage and recovery due to delayed neurotoxicity of DEF. Based on our existing experimental data regarding the late acute effect of orally adminstered DEF, the effect on hematological parameters will be studied to evaluate their usefulness and practicalbility for early diagonsis of late acute effect. The involvement of iron-containing enzymes in the mechanism of late acute effect will be investigated. The proposed study will investigate the antagonistic effect of oxidized glutathione on the late acute toxicity produced by orally-administered DEF. Also, the potentiating effect of a "no-effect" dose of EPN (O-ethyl O-4-nitrophenyl phenylphosphonothioate) will be evaluated. The pharmacolinetics and metabolism of orally and topically-applied DEF will be studied.